Evidence map›Paper›PMID 41744757›Full record

ArticleCells2026

Disruption of Cell-Adhesion Signaling Resolves Unwanted Progenitor Specification in Stem Cell-Derived α and β Cell Grafts.

Kyle R Knofczynski, Ethan W Law, Sean Lewis-Brinkman, Zenith Khashim, Anna Marie R Schornack, Swikriti Shrestha, Lauren T Jennings, Quinn P Peterson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kyle R KnofczynskiMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-1001-5380
Ethan W LawMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-7975-1365
Sean Lewis-BrinkmanMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-8449-3417
Zenith KhashimDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Anna Marie R SchornackDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-8991-3882
Swikriti ShresthaMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Lauren T JenningsMayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-7336-517X
Quinn P PetersonDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-8701-0575

Funding

J.W. Kieckhefer Foundation N/AKenneth Aldridge Foundation N/AKhalifa bin Zayed al Nahyan Foudation N/AStephen and Barbara Slaggie Family N/A
6 · The paper itself

Abstract

Directed differentiation protocols have recently been developed to produce stem cell-derived α (SC-α) cells as a potential component of a complete cell-based therapy for T1D, to complement the more widely studied stem cell-derived β (SC-β) cells. Differentiation protocols for SC-β cells produce off-target cell populations implicated in the development of outgrowths in SC-β cell grafts, but outgrowths from SC-α cells have not been explored. This study identifies that engrafted SC-α cells generate outgrowths of similar composition to SC-β cell outgrowths. Both cell types share outgrowth-driving populations marked by SOX9, CDX2, or SOX2. Single-cell RNA sequencing was used to reveal an enrichment in cell-adhesion signaling events in outgrowth-driving populations. Small-molecule inhibition of the Notch pathway was insufficient to disrupt all three outgrowth-driving populations. A comprehensive disruption of cell-adhesion signaling via single-cell dispersion and reaggregation is found to reduce the outgrowth propensity in engrafted SC-α and SC-β cells. Together, these results suggest that disrupting residual progenitor cells with SC-α and SC-β cell clusters can enhance the safety profile of these cell therapy products for T1D therapy.

Indexed as

Cell AdhesionInsulin-Secreting CellsSignal TransductionStem CellsAnimalsCell DifferentiationHumansMiceReceptors, NotchReceptors, Notchcell therapyhuman pluripotent stem cellsislet cell transplantationpost-transplant growthstem cell-derived alpha cells (SC-α)stem cell-derived beta cells (SC-β)

Identifiers

PMID41744757
PMCPMC12940016

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.